tbuckley/cabot-search huggingface dataset:
Abstract 11521: Prevalence of Immortal Time Bias in High-Impact Cardiovascular Publications
Authors: Michelle Samuel, Stephen Kutcher, Leah K Flatman, Buajitti Emmalin, Farida Mahmoud, Saruchi Bandargal, Jay Brophy
Journal: Circulation (2022)

Background: Immortal time bias (ITB) is a consequence of non-uniform time zeros (ie. start of follow-up) between treatment groups, resulting in misclassification or selection bias in observational cohort studies. ITB poses a substantial problem as its presence favors the treatment, leading to an overestimation of the protective effect or an underestimation of the harmful effects of the treatment group compared to the control group. Depending on the amount of person-time misclassified or excluded, the magnitude of bias due to ITB may be substantially greater than other biases, such as confounding. Objective: To determine the prevalence of ITB in observational cohort studies published between 2020 and 2021 in high-impact cardiovascular journals. Methods: Observational cohort studies published in Circulation, European Heart Journal, and the Journal of the American College of Cardiology between January 2020 and December 2021 were screened for inclusion. Cross-sectional studies, case series, case-control, time-series analyses, and survey or surveillance studies were excluded. Two independent reviewers (ie. epidemiologists) evaluated each article for the presence and type of ITB. Results: Of 1,558 screen articles, 154 published articles were eligible for inclusion. Twenty of 154 (13%) publications had ITB present. ITB was most frequently due to misclassification bias (17 of 20 articles, 85%). ITB due to selection bias was present in 5 of 20 (25%) articles. Two articles had ITB due to both misclassification and selection biases. Most studies (75%) with ITB did not have an active comparator group. Among studies with ITB, event-based cohorts were the most frequent (65%), followed by event-exposure based cohorts (15%), and exposure-based (10%) and time-based (10%) cohorts. ITB was present in studies with various exposures, including medications (7), surgeries or procedures (5), devices (4), and diseases (4). Conclusion: A substantial proportion (13%) of published observational cohort studies in high-impact cardiovascular journals had ITB present and may result in an overestimation of treatment effect. As ITB is preventable with study design techniques, researchers need to be cognizant of this bias.
Abstract 11330: Association of Left Ventricular Wall Stress and Incident Heart Failure in Elderly Community Dwelling Individuals
Authors: Audrey White, Debra Dixon, Vineet Agrawal, Evan Brittain, RAVINDER R MALLUGARI, Jonathan Mosley, Quinn Wells, Deepak K Gupta
Journal: Circulation (2022)

Introduction: Greater left ventricular (LV) wall stress is associated with adverse outcomes among patients with prevalent heart failure (HF). Less is known about the association between LV wall stress and risk of incident HF in community dwelling individuals. Methods: Using data from the NHLBI Biologic Specimen and Data Repository Information Coordinating Center, we studied 4,601 participants of the Atherosclerosis Risk in Communities study without prevalent HF who underwent echocardiography at visit 5 (2011-2013). LV end systolic and diastolic wall stress (LVESWS, LVEDWS) were calculated from chamber and wall thickness measures, E/e’ as a surrogate for LV end diastolic pressure, and systemic blood pressure. Incident HF was assessed by cohort surveillance for hospitalized HF through December 31, 2016. The relationship between LVESWS and LVEDWS was examined by Spearman rank correlation. The association between wall stress and risk of incident HF was tested in Cox regression adjusted for demographics, traditional CV risk factors, prevalent CAD and atrial fibrillation, as well as creatinine, NT-proBNP, troponin, triglycerides, C-reactive protein, LV ejection fraction, and LV mass. Results: The cohort was elderly (median age 75 years), predominantly female (58%), with 18% of individuals identifying as black. Median LVESWS and LVEDWS were 48.8 (IQR: 39.3, 60.1) and 18.9 (IQR: 15.8, 22.5) kdynes/cm2, respectively. LVESWS and LVEDWS were modestly correlated (rho = 0.30, p &lt;0.001). Over a median follow-up of 4.6 years, 156 individuals developed incident HF. In multivariable Cox regression mutually adjusted for LVEDWS and LVESWS, each 1-unit increase in LVEDWS significantly associated with an increased risk of incident HF (HR: 1.03; 95% CI 1.01 - 1.06) (Figure), while LVESWS did not (HR: 1.00; 95% CI 0.99-1.01). Conclusions: Among community dwelling elderly individuals, greater non-invasively measured LVEDWS is associated with an increased risk for incident HF.
Abstract 12229: Adipokines Are Linked to Heart Failure Through Metabolic Risk-Dependent and Independent Pathways: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Bige Ozkan, Sui Zhang, Justin B Echouffo Tcheugui, Roberta Florido, VIJAY NAMBI, Erin D Michos, Layla Abushamat, Wendy S Post, Gary Gerstenblith, Roger Blumenthal, Ron C Hoogeveen, Christie M Ballantyne, Josef Coresh, Elizabeth Selvin, Chiadi E Ndumele
Journal: Circulation (2022)

Introduction: Adipokines have metabolic effects and laboratory studies also suggest direct effects of adipokines on the myocardium. However, there are no population-based studies examining heart failure (HF) risk with multiple adipokines in concert. Methods: We conducted a prospective analysis of ARIC Visit 2 (1990-92) participants without HF. Adipokines were categorized into quartiles. “Abnormal” adipokine levels were defined as the top quartile for leptin, resistin, and visfatin, and the bottom quartile for adiponectin and apelin. We compared the prevalence of adipokine abnormalities across body mass index (BMI) categories: normal weight (BMI 18.5-&lt;25 kg/m 2 ), overweight (BMI 25-&lt;30 kg/m 2 ), obesity (BMI 30-&lt;35 kg/m 2 ) and severe obesity (BMI ≥35 kg/m 2 ). We used Cox regression to examine associations for each adipokine and the number of abnormal adipokines with incident HF. Results: Among 10,725 participants (mean age 58, 55% female, 22% Black), higher prevalences of multiple (≥2) adipokine abnormalities were seen with higher BMI (56% of those with severe obesity vs 15% of normal weight). After adjusting for confounders (Table), higher adiponectin and apelin were associated with lower HF risk (Q4 vs. Q1 HR: 0.70, 95%CI: 0.62-0.79; HR: 0.87, 95%CI: 0.78-0.97), and higher leptin and resistin with higher HF risk (Q4 vs. Q1 HR: 2.06, 95%CI: 1.78-2.38; HR: 1.31, 95%CI: 1.17-1.46). Visfatin was not associated with HF. Results were similar when stratified by obesity (BMI ≥30 kg/m 2 ). For leptin and adiponectin, HF associations were attenuated by adjusting for metabolic risk factors, but not for apelin and resistin (Table). Having more adipokine abnormalities was linked to progressively higher HF risk (For 4 vs 0 abnormalities HR: 2.92, 95% CI: 1.95-4.30). Conclusions: Adipokines are linked to HF risk, with some associations mediated by metabolic risk factors and others independent of metabolic risk. Adipokines may be a key mechanistic link between adipose tissue and HF.
Abstract 12046: Patient Characteristics and Use of Oral Anticoagulation Therapy in New-Onset Atrial Fibrillation: Results From a Nationwide Registry Study in Finland
Authors: Alex Luojus, Ossi Lehtonen, Olli Halminen, Jari Haukka, Mikko Niemi, Jaana Kuoppala, Pirjo Mustonen, Jukka Putaala, Miika Linna, Juha Hartikainen, Juhani Airaksinen, Mika Lehto
Journal: Circulation (2022)

Background and Aims: The risk of ischemic stroke associated with atrial fibrillation (AF) can be reduced with oral anticoagulation therapy (OAC). We examined the patient characteristics and nationwide use of OACs in primary and secondary care AF patients. Methods: The Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) -study is a nationwide study of AF patients that combines data from several Finnish health care registers. In this study all new-onset AF patients in Finland from January 2011 to December 2018 with laboratory data were analyzed. Comorbidities and CHA 2 DS 2 -VASc -score were recorded until date of AF diagnosis. First OAC therapies from diagnosis of AF to the end of study were analyzed. For warfarin users with sufficient laboratory data, time in therapeutic range (TTR) was calculated and patient quartiles by TTR were assigned. Results: Of the 130 533 (50.7 % male) new-onset AF patients studied, 96 051 (73.6%) used any OAC medication after AF diagnosis. The used OACs were warfarin (n= 56 857; 43.6%), apixaban (n=16 377; 12.5%) rivaroxaban (n=14 821; 11.4%), dabigatran (n=7 224; 5.5%), and edoxaban (n=723; 0.6%). The mean TTR values in warfarin TTR-quartiles were 32% (0-52%) in the 1 st quartile, 65% (56-72%) in the 2 nd quartile, 77% (72-83%) in the 3 rd quartile and 90% (83-100%) in the highest quartile. Among patients with standard dose of direct oral anticoagulants, the mean CHA 2 DS 2 VASc -score was 2.78 for dabigatran and 3.47 for apixaban. For patients with warfarin the mean CHA 2 DS 2- VASc -score was 3.50 in the highest quartile. The mean CHA 2 DS 2- VASc for patients without any OAC was 3.19. Conclusion: In unadjusted analyses patients with dabigatran had the lowest and patients with apixaban the highest mean CHA 2 DS 2- VASc score. In patients with warfarin, the highest TTR quartile had the lowest mean CHA 2 DS 2- VASc -score and mean TTR of 77%. Contrary to the guidelines, a remarkable number of patients with high CHA 2 DS 2- VASc score remained without any OAC treatment.
Abstract 12156: Small Proline-Rich Repeat Protein 1a is a Significant Functional Target of Microrna-150 in Mouse Hearts and Human Cardiac Fibroblasts
Authors: Satoshi Kawaguchi, Bruno Moukette, Marisa Sepulveda, Il-man Kim
Journal: Circulation (2022)

Background and Aims: Cardiac injury induces dynamic changes in the expression of microRNAs (miRs). MiR-150 is conserved between rodents and humans, and its downregulation is markedly associated with heart failure (HF) severity and outcome in humans. Using systemic and cardiomyocyte (CM)-specific knockout (KO) mouse models, we reported that miR-150 plays a cardioprotective role in part by decreasing CM apoptosis, and that pro-apoptotic small proline-rich protein 1a ( Sprr1a ) is a direct and functional target of miR-150 in CMs. We also showed that Sprr1a knockdown in mice improves cardiac dysfunction and fibrosis post-myocardial infarction (MI), and that Sprr1a is upregulated in mouse cardiac fibroblasts (CFs) isolated from ischemic myocardium. However, the direct functional relationship between miR-150 and SPRR1A in MI and human CF (HCF) activation has never been established. Methods &amp; Results: Here, we demonstrate using a novel miR-150 KO; Sprr1a -hypomorphic ( Sprr1a hypo/hypo ) mouse model that Sprr1a knockdown blunts cardiac dysfunction, damage, inflammation, apoptosis and fibrosis post-MI caused by miR-150 loss. MiR-150 KO; Sprr1a hypo/hypo mice also exhibit decreased pro-fibrotic markers in the infarct areas of hearts as compared to miR-150 KO mice. Our primary adult HCF studies further reveal that SPRR1A is upregulated in HCFs subjected to simulated ischemia/reperfusion, while its expression is downregulated in HCFs by a cardioprotective β-blocker carvedilol, which is inversely associated with miR-150 expression. MiR-150 knockdown in HCFs also increases pro-fibrotic SPRR1A . Lastly, protective roles of miR-150 in HCFs are in part mediated by the functional repression of SPRR1A (See Figure). Conclusions: Our findings delineate a pivotal functional interaction between miR-150 and Sprr1a as a novel regulatory mechanism pertinent to CF activation post-MI. This axis could be a therapeutic target for intervention in ischemic HF and cardiac fibrosis.
Abstract 11467: Novel Identification Strategy to Increase Diversity in Heart Failure Clinical Trials
Authors: Susan C Gilchrist, Joe Ferrell, Ines Pagel-Langenickel, Cheerag Shirodaria, JB Flinders
Journal: Circulation (2022)

Introduction: Women and racial/ethnic minorities remain underrepresented in cardiovascular (CV) clinical trials, thus limiting the generalizability of study findings and the use of novel CV therapeutic testing among those who often have the greatest burden of CV disease. One potential solution is to shift the identification of trial participants from traditional academic centers to large registries. To this end, we tested whether an Emergency Medical Services (EMS) platform could identify patients in the pre-hospital setting who were potential candidates for heart failure (HF) clinical trials. Second, we sought to determine the demographic underpinnings of this population. Methods: The Biospatial platform used EMS electronic patient care reports (ePCR) as the foundational data source. Records of pre-hospital patients with an EMS provider impression of HF were identified through Biospatial’s artificial intelligence algorithm. In a subset of patients, ePCR records in Florida were linked to hospital diagnosis codes utilizing the Florida Health Information Exchange. Results: Between February 1, 2021 and April 30, 2022, we identified 18,198,085 records in the US with a 911 response and patient disposition requiring EMS transport to a local emergency room. There were 63,595 records in which an EMS provider recorded a primary or secondary impression of HF. Of those, 49% were female, 60.3% were White, 22.7% Black, 3.2% Hispanic/Latino, and 13.8% other or unknown. Next, as a test case, the Florida Health Information Exchange was utilized to determine whether an EMS impression of HF was confirmed by a hospital ICD-10 HF code (I50). There were 5363 records in Florida that met the criteria for a 911 call. Of those, 2355 had linked hospital data and 1560 had a populated diagnosis code. Sixty-four percent (64%) of individuals identified by EMS as having HF in the pre-hospital setting received a hospital diagnosis of HF. Conclusion: The utilization of an EMS registry is a novel strategy to identify a diverse population of HF patients for inclusion into clinical trials. Further work is needed to optimize the EMS heart failure algorithm for clinical trial participant identification and to test this strategy for other CV diagnoses such as myocardial infarction and stroke.
Abstract 11135: Association of Digoxin Use With Transplant-Free Survival in Infants Palliated With a Stage I Hybrid Procedure
Authors: Reshma K Reddy, Sinai C Zyblewski, Shahryar M Chowdhury, Justin Godown, Scott M Bradley, Rachel K Duncan, David W Brown, Tyler N Brown, Katherine E Bates, Luann Minich, John M Costello
Journal: Circulation (2022)

Introduction: Digoxin use in patients with single ventricle physiology after stage I palliation (S1P) has been associated with reduced interstage mortality (IM). However, the S1P hybrid procedure comprised a small fraction of the patients in these evaluations. As it is being performed with increasing frequency, data regarding digoxin effects on IM after this procedure are needed. We sought to determine if digoxin prescription at discharge in infants with the S1P hybrid was associated with improved transplant-free interstage survival. Methods: National Pediatric Cardiology Quality Improvement Collaborative registry data from 2008 to 2021 were utilized. Infants discharged home after the S1P hybrid hospitalization were included. Patients were excluded if they had 1) supraventricular tachycardia, 2) death during S1P hospitalization, 3) conversion to Norwood during S1P hospitalization, or 4) remained hospitalized until stage II surgery. The primary outcome was transplant-free survival. Chi-square, Fisher’s Exact, Mann-Whitney U tests and multivariable logistic regression were used to compare patients receiving and not receiving interstage digoxin following S1P hybrid. Results: Of the 259 patients from 45 sites with S1P hybrid, 129 (50%) were discharged home on digoxin. Baseline characteristics including birth weight, gestational age at birth, race/ethnicity, cardiac diagnosis, presence of aortic atresia, noncardiac abnormalities or genetic syndromes, and one or more pre-operative risk factors were similar between groups. IM or heart transplant occurred in 30 (23%) patients in the no digoxin group compared to 18 (14%) in the digoxin group (P=0.06). With multivariate logistic regression analysis adjusting for home feeding route, degree of right ventricular dysfunction, atrioventricular valve regurgitation and oxygen saturation at discharge, home digoxin prescription was independently associated with a lower risk of IM or transplant (adjusted OR 0.49; 95% CI 0.25-0.98; P=0.04). Conclusions: In patients with single ventricle physiology who underwent a S1P hybrid procedure, digoxin prescription at hospital discharge was associated with improved transplant-free survival during the interstage period.
Abstract 12133: Coronary Artery Perforation During Chronic Total Occlusion Percutaneous Coronary Intervention: Incidence, Mechanisms, Treatment and Outcomes
Authors: Spyridon Kostantinis, Bahadir Simsek, Judit Karacsonyi, Khaldoon Alaswad, Oleg Krestyaninov, Dmitrii Khelimskii, Dimitrios Karmpaliotis, Farouc A Jaffer, Jaikirshan Khatri, Paul Poommipanit, Wissam Jaber, Stephane Rinfret, William Nicholson, MITUL P PATEL, Ehtisham Mahmud, MICHAEL KUTUZIS, Ioannis Tsiafoutis, Stewart M Benton, Rhian Davies, Catalin Toma, Jimmy Kerrigan, Elias Haddad, Nidal Abi Rafeh, MD, FACC, Ahmed El Guindy, Omer Goktekin, Olga Mastrodemos, Bavana V Rangan, M Nicholas Burke, Emmanouil S Brilakis
Journal: Circulation (2022)

Introduction: Coronary artery perforation is a feared complication of chronic total occlusion (CTO) percutaneous coronary intervention (PCI). Methods: We analyzed the baseline clinical and angiographic characteristics and procedural outcomes of 10,454 CTO PCIs performed in 10,219 patients between 2012 and 2022. Results: The incidence of coronary perforation was 4.9% (n=503). Patients who experienced coronary perforation were older and were more likely to have had prior coronary artery bypass graft surgery. Procedures that resulted in perforation were more complex, with higher J-CTO and PROGRESS-CTO scores. Technical (66% vs. 87%; p&lt;0.01) and procedural (55% vs. 87%; p&lt;0.01) success rates were lower among perforation cases. The most common site of perforation was the CTO target vessel (66%), the retrograde approach was responsible for the perforation in 47% of the cases and guidewire exit was the most common mechanism of perforation. The proportion of Ellis Class 1, 2, 3 and 3 -“cavity spilling” coronary perforations was 20%, 41%, 28% and 11%, respectively. In 52% of perforations, one or more interventions were required: prolonged balloon inflation (23%), covered stent deployment (21%), coil embolization (6%) and/or autologous fat embolization (4%). Tamponade requiring pericardiocentesis occurred in 69 patients (14%). The incidence of major adverse cardiovascular events (MACE) was higher in perforation cases (18.1% vs. 1.3%; p&lt;0.01). Conclusions: Coronary artery perforation occurred in 4.9% of CTO PCIs performed by experienced operators and was associated with lower technical success and higher in-hospital MACE.
Abstract 12732: Cardiac Sarcoidosis With Elevated Cardiac Troponin Mimicking Acute Myocardial Ischemia
Authors: Bruce Casipit, Hussein Al Sudani, Aman M Amanullah
Journal: Circulation (2022)

Background Cardiac Sarcoidosis (CS) is a disease with variable presentation causing significant morbidity and mortality. Concurrent signs of myocardial injury as evidenced by troponin elevation add to the complexity of an already challenging diagnosis. Case A 48-year-old female with no significant past medical history presented with episodes of presyncope for 2 months. ECG showed a bifascicular block. Troponin I was elevated to 7.29 ng/mL. 2D echo showed Left Ventricular (LV) systolic dysfunction with an LVEF of 40%. Heparin drip was initiated for a possible NSTEMI. Coronary angiography showed no evidence of epicardial coronary artery disease but showed an anomalous right coronary artery which on CT angiogram later showed no hemodynamically significant stenosis. Telemetry monitoring captured intermittent complete atrioventricular blocks. A biventricular implantable cardioverter-defibrillator was inserted. Due to concerns for infiltrative cardiac disease, a cardiac magnetic resonance (CMR) was done showing findings consistent with cardiac sarcoidosis (CS). CT scan of the chest showed radiographic evidence of pulmonary sarcoidosis, however, she declined further invasive workup. She was then started on systemic corticosteroids. 2D echo 6 months later revealed improvement in the LVEF to 55%. Discussion Our case encompasses the variable presentation of CS including cardiac conduction abnormalities and LV systolic dysfunction. Concomitant troponin elevation in CS can mimic myocardial ischemia making the diagnosis more challenging. This highlights the importance of appropriate diagnostic acumen in approaching a case like this. Current guidelines now include non-invasive means for diagnosis including the use of CMR/PET CT, especially since endomyocardial biopsy has a low sensitivity. Treatment strategies aim to mitigate the long-term effects of CS on the heart, however, there is a paucity of data for appropriate pharmacological regimen.
Abstract 11712: Transcatheter Reconstruction of Right Ventricular Outflow Tract After Severe External Compression by a Pseudoaneurysm in an Adult With Tetralogy of Fallot
Authors: Chelsea Takamatsu, Ramzi Ibrahim, Michel T Corban, Scott E Klewer, Michael D Seckeler
Journal: Circulation (2022)

Introduction: Increased survival of adults with tetralogy of Fallot (TOF) has led to the recognition of unanticipated complications. A rare complication after TOF repair is a right ventricle pseudoaneurysm (RV PSA). Often asymptomatic and incidentally found on imaging, the few reports of clinically significant RV PSA were mostly treated surgically. We present an adult with RV PSA after TOF repair treated by a novel transcatheter approach. Case Presentation: A 41 year old male with TOF and a valved right ventricle to pulmonary artery conduit presented with right ventricular failure due to right ventricular outflow tract obstruction (RVOTO) from an anterior RV PSA compressing the conduit (Figure 1). His case was further complicated by HFrEF, severe pulmonary regurgitation, and refractory atrial fibrillation requiring anticoagulation. Surgical intervention was not offered due to five prior sternotomies; he was not a transplant candidate due to substance abuse. CT imaging was used to create a virtual 3D model for interventional planning (Figure 1). A Covered CP Stent™ (B. Braun, Bethlehem, PA) on top of a Palmaz™ XL 5010 stent (Cordis Corp, Miami Lakes, FL) was anchored in the pulmonary valve ring and extended proximally to seal the PSA leak in the RVOTO, followed by Sapien S3 valve (Edwards, Irvine, CA) implantation in the proximal end of the stents (Figure 2). Right ventricular systolic pressure acutely decreased with improved systolic function. Conclusion: Adults with congenital heart disease often require unique approaches to intervention for managing the unnatural history of their conditions. 3D modeling of complex structures is a vital tool to plan these interventions.